1. Field of the Invention
The present invention relates generally to a unique O-substituted hydroxylamine free base. More particularly, the O-substituted hydroxylamine preferably exhibits at least one property selected from the group consisting of: essentially free of hydroxylamine; essentially free of any solvents; a purity above 98% by gas chromatographic area; a water content of between about 0% to 90% by weight; and a high strength (as measured by mole of the O-substituted hydroxylamine per gram of sample) of between about 0.5 to 3.3-fold as much as a 40% O-substituted hydroxylamine salt solution, by weight. The O-substituted hydroxylamine free base is particularly useful in forming an herbicidal composition which can be used for controlling the growth of vegetation.
2. Discussion of the Background Art
O-(3-Chloro-2-propenyl)hydroxylamine (CPHA), especially trans-isomer, or its salts is an important intermediate for a number of herbicides. This compound has always been prepared in its salt form, especially its hydrochloride (CPHA-HCl). One concern is that the CPHA salts contain significant amount of hydroxylamine, which is more reactive with ketones or aldehydes to form undesirable impurities. Some of these impurities are restricted by the United States Environmental Protection Agency (EPA). Another concern is that CPHA-HCl salt solution is unstable. Refrigeration is always required to maintain temperature below at least 15° C., otherwise substantial decomposition occurs. For example, the commercially available 40% CPHA-HCl solution decomposes by more than half (e.g., 52%) after 23 days at 35° C. Further more, CPHA salts have a limited solubility in water. The practical concentration is about 40%, which is close to its saturation. This limited concentration results in not only a lot of transportation of water, but a lot of brine waste generated in the neutralization step in their application as well. Besides hydroxylamine, there are a number of other significant impurities in the solutions of CPHA salts. Some of them may compete with CPHA in the reactions to form new impurities. The users may suffer a yield penalty.
Commercially available 40% CPHA-HCL solutions have the following deficiencies: (a) contain about 1000 ppm hydroxylamine which reduces oximation yield, but are constrained by regulatory permits as well; (b) contain 0.5 equivalents of hydrochloric acid, which generates a large waste stream during commercial applications; (c) limited to applications where water presence is tolerated; (d) maximum solubility is about 45%, leaving a lot of transportation of water; (e) maximum feasibility concentration is 40%; and (f) contain 2–3% by weight of organic impurities, which may be carried over to end-products or generate new impurities in their applications.
O-substituted hydroxylamine salts can be prepared by oximation of a carbonyl compound, such as acetone, benzaldehyde, 2-butanone with hydroxylamine sulfate or hydrochloride in the presence of sodium hydroxide, followed by alkylation with an alkylating agent that bears the desired functional group. The alkylated oxime is then subject to hydrolysis catalyzed by an acid to form O-substituted hydroxylamine salt. In particular, the O-substituted hydroxylamine relevant to this invention is O-(3-chloro-2-propenyl)hydroxylamine. The preferred acid is hydrochloric acid. The obtained O-(3-chloro-2-propenyl)hydroxylamine hydrochloride (CPHA-HCl) in the art usually contains a number of significant impurities, including hydroxylamine in the range from 300 to 1500 ppm (parts per million) or about 0.33 to 1.64 mole %. Most of these impurities, especially hydroxylamine, have a significantly negative affect in the applications.
O-alkylhydroxylamines in their salt form have been prepared by reacting oximes with alkyl halides under basic conditions to give O-alkyl oximes, followed by acid catalyzed hydrolysis of the O-alkyl oxime. For example, PCT Application WO 8911473 discloses a process for producing O-substituted oxime compounds in which a large excess of propanone oxime in toluene is reacted with an aqueous alkali metal hydroxide to give, after azeotropic distillation, the oxime salt which on reaction with an alkyl halide followed by further distillation, acidification and extraction with toluene affords the O-alkyl oxime in moderate purity (83.5%). European Pat. No. 85-103052 discloses a similar process for the synthesis of O-alkyl oximes which were subsequently hydrolyzed using aqueous hydrochloric acid to give the O-alkylhydroxylamines.
Jap. Pat. No. 03258757 discloses a process in which acetone oxime is reacted with sodium hydride in N,N-dimethylformamide at 60° to 70° C. and the resulting oxime salt subsequently reacted with an alkyl bromide to give a low yield (37%) of an O-alkyl acetone oxime. Jap. Pat. No. 83-68791 discloses a similar process in which the acetone oxime salt is generated below 10° C. and subsequently reacted with a solution of an alkyl halide in dimethoxyethane to give a low yield (52.4%) of an O-alkyl oxime.
German Pat. No. 86-3631071 discloses a procedure for the preparation of O-substituted hydroxylamine hydrochlorides in which an O-alkyl acetone oxime, present in a mixture of 1,4-dioxane, water and hydrochloric acid, is hydrolyzed and the acetone continuously removed by distillation through a bubble tray column.
U.S. Pat. No. 5,488,162 discloses a process for preparing aqueous solutions of O-alkylhydroxylamine salts. The process involves converting hydroxylamine salts to their O-alkyl derivatives without the isolation of intermediates. More specifically, the process involves three steps. The first step, Step (A), involves forming a ketoxime. The second step, Step (B), involves adding an alkylating agent to the ketoxime formed in Step (A). The third step, Step (C), involves hydrolyzing the alkylated ketoxime formed in Step (B) to yield an O-alkylhydroxylamine salt. O-alkylhydroxylamine salts are important intermediates in the preparation of herbicides.
U.S. Pat. No. 5,557,013 demonstrates the preparation of O-substituted hydroxylammonium salts of the following formula:H2NORxHXwhere R is a C1–C6-alkyl or C2–C6-alkenyl radical, each of which may be halogen-substituted, and X is chlorine or bromine, by reacting in an integrated process, without isolation of intermediates. The reaction steps include (a) reacting acetone with hydroxylammonium sulfate and sodium hydroxide solution to give acetone oxime; (b) treating the solution of acetone oxime thus obtained with sodium hydroxide solution and completely removing water; (c) reacting the suspension of the acetone oxime Na salt thus obtained with alkylating agents at from 0.5 to 15 bar and at up to 140° C. to give acetone oxime ethers; and (d) cleaving the acetone oxime ethers with acids HX to give the products I, a homogeneous, nonpolar aprotic solvent being used in all process steps (a) to (d).
Yet another conventional process is described in U.S. Pat. No. 5,585,520 for the preparation of O-substituted hydroxylammonium salts having the following formula:R1—CHX—O—NH2.HL(L=halogen, hydrogensulfate; X═H, alkyl; R1=unsubstituted or substituted phenyl, thienyl, furanyl, pyrrolyl or —CR2═CR3R4; R2, R3, R4═H, halogen or alkyl) by reaction of an acetone oxime O-allyl or —O— benzyl ether of the following formula:
with water and a mineral acid H-L with continuous removal of the acetone formed in this process, by carrying out the hydrolysis batchwise at 0°–50° C. and under a pressure of 10–500 mbar.
Neither preparation nor applications of solvent-free CPHA free base or aqueous CPHA solution has been reported in the prior art. It has been unexpectedly found by the present inventors that CPHA free base according to the present invention is much more stable than its salt solutions. For example, a commercial 40% CPHA-HCl solution decomposes by 52% after 23 days at 35° C., whereas, a 85% CPHA aqueous solution has only 1.1% purity drop after 78 days at 40° C. Unlike CPHA-HCl product, which requires a refrigerated warehouse and refrigerated transportation, free base CPHA according to the present invention does not need refrigeration unless the storage time is over six months or the ambient temperature continuously exceeds 45° C.
The free base CPHA produced by the methods described in the present invention provides a superior quality. It is essentially free of hydroxylamine. It can also be essentially free of those impurities existing in the CPHA salts produced via the conventional processes discussed above. The term “essentially free of” as used herein means that those impurities become non-detectable by gas chromatography (GC), e.g., weigh 1.81 g of 51% by weight of CPHA free base aqueous solution in a vial containing 2.18 g of cyclohexanone; stir the mixture in the capped vial at 50° C. for 2 hours; after cooling, add 8.0 g of dichloromethane and shake for one minute; settle for 5 minutes; gas chromatographic (GC) analysis of the organic phase indicates 0.00% area for cyclohexanone oxime, which indicates that there is no hydroxylamine in the sample.
Free base CPHA is miscible with water at room temperature, hence one can produce any concentration of CPHA from very dilute to near 100% based on the present invention. The preferred free base CPHA concentration of the present invention is between about 50–55%, by weight, which has about 70–80% more strength than the conventional 40% CPHA-HCl solution. A 99% purity of solvent-free CPHA of the present invention is about 3.3 times as effective as 40% CPHA-HCl solution.
A high purity CPHA produced via the present invention is superior in pharmaceutical applications, where even a 0.1% level impurity can affect the process significantly. One can also produce a free base CPHA solution in any suitable solvents for customized applications based on the present invention. This is extremely important for pharmaceutical and agricultural applications because hydroxylamine is more reactive than CPHA, thereby reducing yield and generating undesirable impurities. Moreover, the aqueous free base CPHA according to the present invention has no inorganic substances and is therefore particularly useful for pharmaceutical and agricultural applications. Finally, the solvent-free CPHA free base according to the present invention can have a concentration of 100% or less, thus one pound of 100% CPHA free base is equivalent to 3.35 pounds of conventional 40% CPHA-HCl salt solution.